PXD022002

PXD022002 is an original dataset announced via ProteomeXchange.

Title	Structure of the human signal peptidase complex
Description	The ER-resident signal peptidase complex (SPC) is an essential membrane protein complex involved in the maturation of soluble and type-I transmembrane proteins destined to the secretory pathway. As a part of the ER translocon machinery, the SPC removes signal peptides (SPs) from the N-termini of many proteins such as hormones, antibodies, or secretory enzymes1,2. To accomplish this task, the SPC must process a large variety of SPs with an exquisite specificity. Although the determinants of SP recognition have been established empirically3, the molecular details of SP recognition and removal remain elusive. Here, we show that the human SPC exists in two functional paralogs with distinct proteolytic subunits. We determined the structures and posttranslational modifications of both paralogs using electron cryo-microscopy and structural proteomics. The respective proteolytic subunits SEC11A and SEC11C adopt a conserved signal peptidase (SPase) fold with their active sites facing a prominent transmembrane window, which is collectively formed by the transmembrane domains of all SPC subunits. Characteristic, charged regions on both sides of this window locally thin the membrane by approximately 40% compared to the exterior. The data suggest a mechanistic model for SPC specificity and the transfer of SPs from the Sec61 translocation channel to the SPC.
HostingRepository	PRIDE
AnnounceDate	2021-07-05
AnnouncementXML	Submission_2021-07-04_22:13:30.543.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Barbara Steigenberger
SpeciesList	scientific name: Bos taurus (Bovine); NCBI TaxID: 9913; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-15 03:55:39	ID requested
⏵ 1	2021-07-04 22:13:30	announced

Dataset with its publication pending

submitter keyword: Signal Peptidase Complex, cryoEM, Crosslinking MS

Richard A. Scheltema
contact affiliation	Netherlands Proteomics Centre, Biomolecular Mass Spectrometry and Proteomics
contact email	R.A.Scheltema@uu.nl
lab head
Barbara Steigenberger
contact affiliation	Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University
contact email	B.A.Steigenberger@uu.nl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/07/PXD022002

PRIDE project URI

• PRIDE
  1. PXD022002
     1. Label: PRIDE project
     2. Name: Structure of the human signal peptidase complex